For the last five years I have been involved in two, rather different, areas of research. The first is a study of the biochemical processes involved in learning, analyzing learning and memory mutants of Drosophila melanogaster. Drosophila can learn. They exhibit time-associative learning in several behavioral tests: They will selectively avoid odors previously associated with electric shock or will show a preference for odors previously associated with a sucrose reward. Five single gene mutations in Drosophila have been isolated which either abolish learning in these tests or shorten memory. Research in many other systems, both vertebrate and invertebrate, has suggested that modulation of intracellular cyclic AMP levels plays an important role in behavioral plasticity. Results with Drosophila support this idea: Three mutants that do not learn have defects that directly or indirectly alter cyclic AMP metabolism. This project will initially focus on one learning mutant, rutabaga, with a defect in the enzyme adenylate cyclase. Biochemical and genetic studies of this mutant should yield information about the enzyme itself and how it is involved in behavioral plasticity. We will also use specific biochemical selection screens to isolate other mutants in this pathway and characterize them. The second project is a collaboration and represents continuation of work begun in 1979. The immediate objective of these studies is to determine the anatomical connections and physiological significance of certain cytochrome oxidase dense structures in primate areas 17 and 18. We have already shown that cells in the densely staining blobs of area 17 are concerned with color, that they are closely interconnected in 17, and are specifically connected to the thinner of two sets of densely staining stripes in 18. We plan to examine these connections in more detail, using axonal transport methods, and to extend our recent physiological studies to area 18, to learn how the color information is further processed in the thin stripes. We have strong hints that the thicker stripes are concerned with stereoscopic depth perception, and plan to examine this further. One long-range objective is to find out more about the effects of neuromodulators in mammalian central nervous systems. A study on the influence of sleep and arousal in area 17 will be continued and extended, within the next year or so.